Stem cells such as ES cells and iPS cells, which are derived from a human, have ability to differentiate into various kinds of cells and may be applied to large-scale efficacy evaluation or medical treatment using human cells, such as resolution of disease or, drug discovery screening, a toxicity test, and regenerative medicine, which have been difficult to achieve so far, and thus have attracted attention. It is considered that the differentiation efficiency when differentiation is induced from these stem cells into target cells greatly depends on the state of stem cells which are a starting material. That is, when stem cells do not maintain an undifferentiated state while maintaining pluripotency, the efficiency of differentiation induction is reduced. For that reason, for an industrial application of these stem cells, it is extremely important to manage the quality of stem cells in a process of culturing stem cells, and it is necessary to monitor stem cells and determine the state thereof. Further, in the management process, it is necessary to non-invasively determine the cells while being cultured. In addition, these stem cells form a colony (a cell population formed by several thousand to several tens of thousands of cells), and thus there is a need for a technology for determining the quality in a state of colony. The colony is not always formed by cells with uniform quality, and the cell characteristics vary from site to site. For that reason, it is preferred to obtain information, such as a map, which is capable of determining the distribution of the cell state inside the colony by using, as an index, the state of individual cells constituting a colony.
Patent Literature 1 discloses a cell-image analyzing apparatus that analyzes a cell image, determines, to be specific, in a region in which regions forming a colony and regions not forming a colony coexist, the regions forming a colony, and acquires information such as position and size of the regions forming a colony. In particular, single-cell regions forming a colony have a shape approximate to a circle, and thus a colony region is distinguished from a non-colony region in accordance with circularity (a value which is small when the shape is a circle, and increases when the shape deviates from the circle).
In an apparatus for determining a cell state which is described in Patent Literature 2, a device for determining an active state of floating cells first acquires an image of floating cells from viewpoint that the better the cell state is, the more approximate to a circle the floating cells are, and the worse the cell state is, the stronger the ellipticity is or the more distorted the shape becomes. Next, a contour of floating cells in the acquired phase image is extracted, and it is determined how approximate to a circle the extracted contour of floating cells is.
In a device for evaluating a culture solution, which is described in Patent Literature 3, a living cell and a dead cell are distinguished by comparing the intensities of light at the inner side of a cell and the edge of the cell using the polarization characteristics of cells. In particular, it is described that in a living cell, the inner side of the cell is dark and the outer side of the cell is bright, and it is also described that it is possible to acquire an image having a high contrast when using a phase contrast microscope.